The present invention relates to multilayer elastomer films (multilayer material) comprising at least one continuous layer carrying active chemical substance (such as corrosion inhibitors, lubricants or alternatively biocides with a medical use) inserted between inert elastomer barrier layers; it also relates to the processes for the preparation and to the various applications of these films.
The various elastomer materials commonly used in the medical or paramedical field can be modified so as to be combined with active chemical substances having a protective effect during the use of these materials (gloves, fingerstalls, condoms, and the like), as illustrated in European Patent 306,389 or International Application WO 95/17453, on behalf of the Applicant Company, which describe elastomer films enclosing a dispersion of at least one active chemical substance, which dispersion being either in the liquid form (International Application WO 95/17453) or contained in microcapsules, the walls of which are ruptured under the effect of frictional or shear forces (European Patent 306,389).
However, the preparation of elastomer films according to the methods described in the above-mentioned applications and patents exhibits a number of disadvantages, which relate either to the product itself, that is to say the film, or to the process for obtaining the film.
disadvantages related to the product:
the major disadvantage of the films according to either of the two abovementioned methods is the non-homogeneity of the distribution of the active chemical substances within the polymeric material, due to the fact that the chemical substance is dispersed in the polymeric material in the form of droplets or microcapsules.
This non-uniformity in the distribution of the active chemical substances is reflected by gaps in active chemical substance, which constitute a risk in the context of the desired protection, even if this risk is statistically very low;
the microcapsules contained in the elastomer films according to European Patent 306,389 can exhibit difficulties in rupturing, to release their active substances, during the perforation of the said films;
the elastomer films containing liquid inclusions according to International Application WO 95/17453 involve macromolecular stabilizers of grafted or sequenced copolymer (block copolymer) type which are relatively expensive.
disadvantages related to the process:
in the case of International Application WO 95/17453, the preparation of films from a dispersion of active chemical substance is conditioned by the stability of the bath containing the dispersion, itself a function of the active substance (virucide, for example) content, which constitutes a limiting factor;
likewise, in U.S. Pat. No. 306,389, the production of microcapsules, of controlled size, requires the use of a complex process, particularly as regards controlling the thickness and porosity of the wall;
the preparation of films according to either of the two methods is accompanied, in all cases, by emission of organic vapours; indeed, the elastomers are always used in more or less concentrated solution form in organic solvents.
Consequently, on continuing its research, the Applicant Company has set itself the aim of developing a new type of elastomer material corresponding better to practical requirements than the array of elastomers of the prior art, in particular in that it includes at least one active chemical substance, in the desired proportions, in the form of a continuous layer and not of a dispersion or of an emulsion, which makes it possible to avoid the problems related to the dispersion and/or emulsification stage (stability of the emulsion bath, expense of the stabilizing polymers, presence of gaps), and in that it makes it possible to obtain a flexible and elastic multilayer material which is particularly well suited to the preparation of gloves, fingerstalls or condoms from which the active substance x is only released in the event of the material tearing.
Moreover, the process for the preparation of the material according to the present invention can be carried out entirely or partially in aqueous medium.
The subject of the present invention is a multilayer polymeric film (multilayer material), characterized in that it comprises at least one layer A composed of a gel which is reversible or non-reversible, as a function of the temperature, and which carries at least one active chemical substance x, and at least two barrier layers E comprising a synthetic elastomer e, the said layers being held together by a polymeric bonding agent y incorporated in at least one of the said layers A or E and/or by an independent bonding layer Z comprising a polymer z and/or by chemical or physical treatment of at least one of the said layers A or E.
Chemical treatment is understood to mean either a grafting or a chemical attack using an acid, for example sulfuric acid, and physical treatment is understood to mean a bombardment of the surface of the film with ions or electrons: corona or plasma treatment, or photons: ultraviolet treatment.
Gels which are non-reversible, as a function of the temperature, are formed chemically, that is to say by crosslinking by covalent bonding, which takes place by addition of a crosslinking agent ic (irreversible crosslinking agent) and/or by thermal or photochemical activation, such as, for example, under the effect of ultraviolet radiation, whereas gels which are reversible as a function of the temperature are formed either physically, that is to say by interaction of hydrogen bond, Van der Waals or dipole-dipole type or by formation of crystalline domains or complexes. Such reversible gels can also, in certain cases, involve a crosslinking agent rc (reversible crosslinking agent).
In the case of reversible gels, a transition takes place at a critical temperature (Ttrans) at which the physical interactions disappear; the gel-liquid transformation corresponds to this temperature.
According to an advantageous embodiment of the said layer A, when it is composed of a reversible gel, the latter essentially comprises a structuring polymer c, at least one active chemical substance x and a solvent sa; in addition, it can contain a bonding agent y and a reversible crosslinking agent rc. The combination forms a flexible and elastic layer A.
In certain cases, the structuring polymer c also acts as solvent sa.
According to an advantageous arrangement of this embodiment, the said reversible gel exhibits a gel-liquid transition temperature (Ttrans) of between 0xc2x0 C. and 120xc2x0 C., preferably of between 20xc2x0 C. and 85xc2x0 C. and more particularly between 20xc2x0 C. and 700xc2x0 C.
According to another advantageous arrangement of this embodiment, the structuring polymer c of the layer A is a polymer which is immiscible with the elastomer e, preferably of hydrophilic type and compatible with the active chemical substance, alone or in solution in a solvent sa.
According to an advantageous form of this arrangement, the structuring polymer c is selected from the group consisting of synthetic polymers of acrylic or vinyl type, such as poly(acrylic acid) and polyvinyl alcohol, or of natural origin, such as gelatin, gums, pectin, alginates, polypeptides, polyureas, heparinoids and poly(gluconic acid), as well as certain cellulose derivatives, such as methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and carboxymethyl cellulose, or certain starch derivatives and crystallizable or partially crystallizable polymers, such as, for example, polyethers.
According to another advantageous arrangement of this embodiment, the crosslinking agent rc is selected from the group consisting of (i) certain boron derivatives, such as boric acid or borax, (ii) certain divalent metals, such as zinc or calcium, and (iii) certain trivalent metals, such as aluminium, in alumina hydrate, aluminium sulphate or certain aluminium hydroxides, or chromium, in chromium oxide; it is used as crosslinking agent for the structuring polymer c preferably containing hydroxyl functional groups, such as polyvinyl alcohol, and acts by formation of physical bonds between the chains of the structuring polymer c.
According to another advantageous embodiment of the said layer A, when it is composed of a non-reversible gel, the latter essentially comprises a structuring polymer c, a crosslinking agent rc, at least one active chemical substance x and a solvent sa; in addition, it can contain a bonding agent y. The combination then forms a flexible and elastic layer A.
In certain cases, the structuring polymer c also acts as solvent sa.
According to an advantageous arrangement of this embodiment, the structuring polymer c is a polymer which is immiscible with the elastomer e, preferably of hydrophilic type and compatible with the active chemical substances x, alone or in solution in a solvent sa.
According to an advantageous form of this arrangement, the said structuring polymer c is selected from the group consisting of (i) polymers of natural origin, such as gelatin, gums, pectins, alginates, polypeptides, polyureas, heparinoids and poly(gluconic acid) or certain cellulose derivatives, such as methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and carboxymethyl cellulose, or certain starch derivatives and (ii) synthetic polymers, such as polyethyleneimine, poly(acrylic acid), polyvinyl alcohol, which are alone or as interpenetrated networks, polyacrylamides and their derivatives, polyvinylpyrrolidone, polydimethylsiloxane or poly(vinyl ethers) such as poly(vinyl methyl ether).
According to another advantageous arrangement of this embodiment, the crosslinking agent ic is selected, for the polymers c containing hydroxyl functional groups, from aldehydes or dialdehydes of low or high molecular weight, such as, for example, glyoxal, or other compounds, such as urea-formaldehyde or melamine-formaldehyde derivatives, and, for the polymers containing hydroxyl, carboxyl or amine functional groups, from prepolymers containing isocyanate functional groups and generally from any other compound capable of reacting chemically with the structuring polymer c.
In accordance with the invention, the layer A additionally comprises, whatever the gel (reversible or non-reversible):
at least one active chemical substance x, selected from compounds capable of causing virtually instantaneous denaturation of proteins on simple contact, either by chemical reaction or by a physico-chemical effect, such as by modification of the surface tension. This family of compounds comprises, inter alia, biocides; the said active chemical substance x must be suitable for the structuring polymer c and for the other constituents of the layer A, in order to avoid any possibility of chemical reaction between them.
According to an advantageous arrangement, the said active chemical substance is a quaternary ammonium, preferably dimethyldidecylammonium (Bardac(copyright)), biguanides, phthalaldehyde, phenol derivatives, formaldehyde, non-ionic surfactants containing at least one polyoxyethylene sequence, hexamidine, iodinated compounds, for example the polyvinylpyrrolidone-iodine complex, non-ionic surfactants with a virucidal activity, sodium and potassium dichromates and hypochlorites or charged polymers, such as polyelectrolytes exhibiting biocidal activities, such as poly(acrylic acid), poly(divinylbenzyltrimethyl-ammonium chloride), the divinyl ether-maleic anhydride copolymer, polyethyleneimines, polyetheramines, polyureas and polypeptides, which are used alone or as mixtures.
In certain cases, the active chemical substance x also acts as solvent sa.
a solvent sa, selected from the group consisting of (i) compounds of low volatility, such as polyols, preferably from ethylene glycol, propylene glycol or glycerol, and more generally polyethylene glycols which are liquid at room temperature and with a molecular mass of between 62 (ethylene glycol) and 750 daltons (PEG 750), or water when it is included in the structuring polymer c, (ii) volatile solvents, such as alcohols or ketones of low molecular weight, non-cyclic or cyclic ether compounds, such as tetrahydrofuran, (iii) dimethyl-formamide or dimethyl sulphoxide, or (iv) water (elimination by evaporation), which are used alone or as mixtures.
The layer A, in addition, optionally comprises:
a bonding agent y, chosen from polymers containing both at least one poly A sequence compatible with the layer A and at least one poly E sequence compatible with the layer E which are selected from the group consisting of di-block copolymers, of poly A-block-poly E type, tri-block copolymers of poly E-block-poly A-block-poly E (EAE) type, of poly A-block-poly E-block-poly A (AEA) type, of poly A-block-poly E-block-poly F (AEF) type or of poly A-block-poly F-block-poly E (AFE) type, and grafted copolymers of poly A-grafted-poly E or poly E-grafted-poly A type or of poly A-grafted-poly E and -poly F type, it being possible for the poly F sequence to be compatible with the layer A or with the layer E, or from adhesives of acrylic, silicone or polyurethane type.
The poly A sequences are chosen from the group which comprises polyoxyethylene, polyvinylpyridine, poly(acrylic acid)s, polyvinyl alcohol and quaternized polyvinylpyridine and the poly E sequences are chosen from the group which comprises polydienes, polyolefins, polyoxypropylene and polydimethylsiloxane.
As examples of polydienes or polyolefins, the following may be cited: polybutadiene, polyisoprene, hydrogenated polybutadiene, hydrogenated polyisoprene, polystyrene or poly-4-tert-butylstyrene.
Mention may in particular be made, among the grafted structures containing poly A, poly E and poly F sequences, of:
as poly F sequences, acrylic chains, for example,
as poly E sequences, alkyl chains, for example, and
as poly A sequences, polyoxyethylene chains, for example.
These structures correspond to certain grafted polymers sold by the company Goldschmidt under the trade name xe2x80x9cBrinoil LE(copyright)xe2x80x9d.
According to another embodiment of the said multilayer material, the said gel layer A comprises:
when the gel is reversibly crosslinked:
between 0 and 98%, preferably between 25 and 98%, of solvent sa with respect to the gel,
between 0.1 and 74%, preferably between 1 and 74%, of structuring polymer c with respect to the gel,
between 1 and 80%, preferably between 1 and 74%, of the said active chemical substance x with respect to the gel and
between 0 and 0.1% of crosslinking agent rc crosslinking agent content by mass/combined cibstutyebts);
when the gel is non-reversibly crosslinked:
between 0 and 98%, preferably between 25 and 98%, of solvent sa with respect to the gel,
between 0.1 and 74%, preferably between 1 and 74% of structuring polymer c with respect to the gel,
between 1 and 80%, preferably between 1 and 74%, of the said active chemical substance x with respect to the gel and
between 0.0001 and 0.1% of crosslinking agent ic (crosslinking agent content by mass/combined constituents).
A bonding agent y can be added in proportions by mass of 0.01 to 25% with respect to the gel; the proportions of solvent sa are consequently adjusted.
Also in accordance with the invention, the said multilayer material comprises, as layer E, a synthetic elastomer e, selected in a non-limiting way from polybutadiene, polyisoprene, acrylic polymers, polychloroprene, polyurethane, copolymers based on chlorobutadiene and methacrylic acid or based on ethylene and vinyl acetate, or SBR (Styrene Butadiene Rubber), SBS (styrene-butadiene-styrene), SIS (styrene-isoprene-styrene) or SEBS (styrene-ethylene-butylene-styrene) copolymers, and optionally a bonding agent y as defined above.
The elastomer e can be used either in the form of a solution in an organic solvent sa or in the form of an aqueous dispersion (latex).
Also in accordance with the invention, the said multilayer material comprises, as bonding layer Z, a polymer z selected from the group consisting of (i) the di-block, tri-block or grafted copolymers described in the preceding arrangements (copolymer used as bonding agent y), (ii) polymers of acrylic or vinyl type, such as, for example, vinyl acetate or vinyl laurate, (iii) diene polymers containing nitrile functional groups, such as NBR (nitrile-butadiene-rubber), polyurethanes and certain polyesters or polyamides and (iv) copolymers of the same type as those selected for the layer E, which are treated in order to render them compatible with the layer A, either chemically by grafting, such as SEBS treated with maleic anhydride, or by chemical attack of SBS or SIS with a sulfuric acid solution, or alternatively physically, by bombardment of the surface of the film using ions or electrons: corona and plasma treatment, or with photons: ultraviolet treatment.
The polymer z can be used either in the form of a solution in an organic solvent sa or in the form of an aqueous dispersion (latex).
Such polymeric films or multilayer materials, formed from at least one continuous gel layer A, optionally containing a bonding agent y, and from at least two elastomer barrier layers E, optionally containing a bonding agent y, which are held together using the said bonding agent y and/or using an independent bonding layer Z, exhibit, unexpectedly, a flexible and elastic structure which is particularly well suited to the preparation of gloves, fingerstalls or condoms. The latter provide the wearer of the said material, in particular during medical examinations or surgical operations or in dentistry, with effective protection against infectious agents which are transmittable by the blood, in particular in the event of tearing or even simply of splits in the elastomer membrane which could result in contamination of the wearer of the said material, the use of which is therefore not without risk in the absence of the multilayer material according to the invention.
Another subject of the present invention is processes for the preparation of a multilayer material according to the invention comprising at least one layer A composed of a reversible gel, as defined above, and at least two barrier layers E comprising a synthetic elastomer e, the said layers being held together by a polymeric bonding agent y incorporated in at least one of the said layers A or E and/or by an independent bonding layer Z comprising a polymer z:
The xe2x80x9creversible gel layer Axe2x80x9d process {circumflex over (1)} comprises:
1) the preparation of a first elastomer barrier layer E, which may or may not carry bonding agent y, by dissolution of a polymer e, as defined above, in a solvent se, selected from the group consisting of (i) aromatic, aliphatic and alicyclic hydrocarbons, for example paraffin hydrocarbons, cyclohexane, benzene, toluene, xylene, tetralin or decalin, (ii) petroleum fractions, (iii) other more polar solvents, such as alcohols or ketones of low molecular weight, (iv) non-cyclic or cyclic ether compounds, such as tetrahydrofuran, (v) water, or (vi) dimethylformamide or dimethyl sulphoxide, which are used alone or as mixtures, spreading the said solution over an appropriate substrate and evaporation of the solvent se; the film-forming can be accompanied by a crosslinking stage, such as, for example, a vulcanization. The solvent is water in the case where the polymer e is used in the form of a dispersion (latex);
2) the preparation of at least one layer A according to the following process, when the gel is formed spontaneously by bonds of physical type;
preparation of a solution by mixing at least one active chemical substance x, optionally in a solvent sa, with a structuring polymer c and optionally a bonding agent y at a temperature greater than the transition temperature Ttrans corresponding to the gel-liquid transition, which temperature Ttrans is between 20xc2x0 C. and 120xc2x0 C. (film-forming of the mixture), followed by
spreading the said solution over the layer obtained in Stage 1) and cooling to a temperature of less than Ttrans; the film-forming can be accompanied by emission of solvent sa;
3) the spreading of a succession of layers A and E according to a desired order, which layers A and E are optionally separated by bonding layers Z and are prepared in accordance with Stages 1) and 2) and
4) the preparation and the spreading or a final elastomer barrier layer E which may or may not carry a bonding agent y, by evaporation of the solvent se or water, this stage optionally being followed by a crosslinking stage, such as, for example, a vulcanization.
The xe2x80x9creversible gel layer Axe2x80x9d Process {circumflex over (2)} comprises:
1) the preparation of a first elastomer barrier layer E in accordance with Stage 1) of the xe2x80x9creversible gel layer Axe2x80x9d Process {circumflex over (1)};
2) the preparation of at least one layer A, according to the following process, when the addition of a crosslinking agent rc is necessary for the formation of the reversible gel (crosslinking agent rc introduced simultaneously with the mixture comprising the polymer c):
preparation of a solution by mixing at least one active chemical substance x, optionally in a solvent sa, with a structuring polymer c and optionally a bonding agent y at a temperature greater than the transition temperature Ttrans corresponding to the gel-liquid transition, which temperature Ttrans is between 20xc2x0 C. and 120xc2x0 C.,
introduction, simultaneously with the mixture comprising the structuring polymer c, the active chemical substance x, the solvent sa and optionally the bonding agent y, of a crosslinking agent rc, for example by spraying: the crosslinking takes place rapidly and induces the formation of the film;
spreading the said solution over the layer obtained in 1), followed by cooling and rapid crosslinking;
3) the spreading of a succession of layers A and E according to a desired order, which layers A and E are optionally separated by bonding layers Z and are prepared in accordance with Stages 1) and 2) and
4) the preparation and the spreading of a final elastomer barrier layer E in accordance with Stage 1).
The xe2x80x9creversible gel layer Axe2x80x9d Process {circumflex over (3)} comprises, in Stage 2), the incorporation of the crosslinking agent rc in a volatile solvent itself forming a film.
Another subject of the present invention is processes for the preparation of a multilayer material according to the invention comprising at least one layer A composed of a non-reversible gel, as defined above, and at least two barrier layers E comprising a synthetic elastomer e, the said layers being held together by a polymeric bonding agent y incorporated in at least one of the said layers A or E and/or by an independent bonding layer Z comprising a polymer z:
The xe2x80x9cnon-reversible gel layer Axe2x80x9d Process {circumflex over (1)} comprises:
1) the preparation of a first elastomer barrier layer E, which may or may not carry bonding agent X, by dissolution of a polymer e in accordance with the invention in a solvent se, as defined above, spreading the said solution over an appropriate substrate and evaporation of the solvent se; and optionally crosslinking;
2) the preparation of at least one layer A according to the following process (incorporation of the crosslinking agent ic directly in the solution):
preparation of a solution by mixing at least one active chemical substance x, optionally in a solvent sa, with a structuring polymer c and optionally a bonding agent y,
incorporation of a crosslinking agent ic directly in the said solution,
spreading the said solution over the layer obtained in Stage 1) (film-forming),
initiation of the crosslinking by the photochemical and/or thermal route or alternatively by contact with a crosslinking accelerator;
3) the spreading of a succession of layers A and E according to a desired order, which layers A and E are optionally separated by bonding layers Z and are prepared in accordance with Stages 1) and 2) and
4) the preparation and the spreading of a final elastomer barrier layer E in accordance with Stage 1).
The xe2x80x9cnon-reversible gel layer Axe2x80x9d Process {circumflex over (2)} comprises:
1) the preparation of a first elastomer barrier layer E in accordance with Stage 1) of the xe2x80x9cnon-reversible gel layer Axe2x80x9d Process {circumflex over (1)};
2) the preparation of at least one layer A according to the following process (introduction of the crosslinking agent ic simultaneously with the mixture);
preparation of a solution by mixing at least one active chemical substance x, optionally in a solvent sa, with a structuring polymer c and optionally a bonding agent y,
introduction, simultaneously with the mixture comprising the polymer c, the active chemical substance x, the solvent sa and optionally the bonding agent y, of a crosslinking agent ic, for example by spraying; the crosslinking takes place rapidly and induces the formation of the film;
spreading the said solution over the layer obtained in Stage 1), followed by rapid crosslinking, inducing the formation of the film;
3) the spreading of a succession of layers A and E according to a desired order, which layers A and E are optionally separated by bonding layers z and are prepared in accordance with Stages 1) and 2) and
4) the preparation and the spreading of a final elastomer barrier layer E in accordance with Stage 1).
In accordance with the invention, the superimposition of various films A prepared with various active chemical substances x makes it possible simultaneously to obtain the effects of the said chemical substances without combining them.
According to an advantageous embodiment of the said processes, the bonding layer Z is prepared by evaporation of the solvent sz or of water from a mixture comprising a polymer z, as defined above, in solution in a solvent sz, selected from the group which comprises aromatic, aliphatic and alicyclic hydrocarbons, more polar compounds, such as ethers such as tetrahydrofuran, ketones, dimethylformamide, dimethyl sulphoxide, or alcohols, and water or a mixture of intermediate polarity.
According to an advantageous arrangement of this embodiment, the bonding layer Z is subjected to a crosslinking initiated photochemically, such as, for example, under the effect of ultraviolet radiation, and accelerated thermally or alternatively chemically, such as, for example, by oxidation or using a crosslinking agent. The solvent is water in the case where the polymer z is used in the form of a dispersion (latex).
As an alternative form, in the case where the said layers are held together by a chemical or physical treatment, the process for the preparation of the said multilayer material comprises, after the spreading of a layer A and/or of a layer E over an appropriate substrate, a chemical or physical treatment as defined above.
As another alternative form, the multilayer material according to the invention comprising a non-reversible gel as layer A comprises a stage of preparation of the structuring polymer c by in situ polymerization from a mixture of one or a number of monomers m and of at least one active chemical substance x, by the thermal route or by the photo-chemical (ultraviolet radiation) or radiochemical (60Co cobalt source) route.
According to an advantageous embodiment of this alternative form, the said mixture additionally comprises at least one of the following additional components: an initiator i, one or a number of solvents sa, a thickener f, a crosslinking agent ic or a bonding agent y.
According to an advantageous arrangement of this embodiment, the said monomers m are preferably selected from the group consisting of acrylates and their derivatives, such as acrylic acid, hydroxyethyl methacrylate or methyl methacrylate, acrylamides, acrylamines and their derivatives, or vinyl pyrrolidone.
According to an advantageous form of this arrangement, the number of monomers used is between 1 and 10, preferably between 1 and 4.
In accordance with this alternative form:
in the case of a polymerization initiated thermally, the initiator i is selected from the group consisting of the family of peroxides, such as benzoyl peroxide, the family of azonitriles, such as azobisisobutyronitrile, or redox pairs, such as the pair s2O8/S2O5;
in the case of a polymerization initiated photochemically, the initiator i is selected from the group consisting of the family of acetophenones, benzoin derivatives or the family of peroxides.
According to another advantageous arrangement of this embodiment, the thickener f is selected from the group consisting of aluminium stearates, calcium linoleata pastes, hydrogenated castor oil, triglycerides, modified clays of bentonite type, polyol esters, silicas and polymers which are compatible with the mixture of monomers or of the same nature as the gelled polymer, such as some modified poly(acrylic acid)s, polymethacrylates or polyvinylpyrrolidone.
Another subject of the present invention is the various applications of the elastomer film according to the invention as coating for substrates, in particular made of elastomer or of plastic (gloves, fingerstalls, condoms, and the like) or for overformering a rubbing seal.